December 16, 2012
HIV Drug Maraviroc Could Help Immune System Battle Staph Infections
redOrbit Staff & Wire Reports - Your Universe Online
In the study, senior author and NYU assistant professor of microbiology Dr. Victor J. Torres and colleagues discovered that maraviroc, an antiretroviral drug used to treat those who have contracted the AIDS-causing lentivirus, could possibly also be used to treat Staphylococcus aureus, a bacteria that can cause a variety of life-threatening conditions, including pneumonia, meningitis, toxic shock syndrome (TSS), and sepsis.
"What are the chances that a drug for HIV could possibly treat a virulent Staph infection?" Dr. Torres said in a statement, adding that the discovery which could help overcome the increasingly antibiotic-resistant pathogen resulted from "a fantastic collaboration that we hope will result in significant clinical benefit."
During that collaboration, Dr. Torres teamed up with NYU associate professor of microbiology and pathology and medicine Dr. Derya Unutmaz to study CCR5, a receptor on the surface of immune T-cells, macrophages, and dendritic cells. Previously, NYU researchers had discovered that the receptor is how HIV gains access to T-cells, and now the two doctors have discovered that CCR5 is also a target of Staph because it can generate the immune system's response to combat the disease-causing agent.
"The scientists discovered that one of the toxins the bacterium releases, called LukED, latches on to CCR5 and subsequently punches holes through the membrane of immune cells, causing them to rapidly die," the university explained. "The LukED toxin belongs to a family of proteins called leukotoxins, encoded and produced by Staph to fight off the immune system's defenses."
"This discovery was made after Dr. Torres asked Dr. Unutmaz and fellow HIV researcher Nathaniel Landau, PhD, professor of microbiology, if he might use some of the human immune cells they had collected over the course of their HIV studies," they added. "Dr. Torres was trying to find out which immune cells were affected by different leukotoxins. Dr. Unutmaz gave him a T cell line, which they were using for their HIV infection studies and had previously engineered to express CCR5, to test the effects of these toxins."
All of the T-cells that contained CCR5 died within one hour of being exposed to LukED, while similar cells that lacked CCR5 were totally immune to the effects of the toxin, Dr. Torres explained. Following that discovery, the professor treated T-cells containing the receptor with maraviroc, then exposed that line of cells to LukeED.
The drug "completely blocked the toxic effects of this leukotoxin at doses similar to those used to inhibit HIV infection," Dr. Unutmaz said, calling the findings "remarkable."
"The researchers further corroborated the critical role of CCR5 in Staph infections using a mouse model," the university added. "When they infected mice susceptible to Staph infection with strains that contain the LukED toxin, almost all the mice died. However, mice that were genetically engineered to lack CCR5 on their cells survived this lethal Staph infection."
The researchers, who have had their work published online in the journal Nature, say that they hope their discovery will ultimately lead to human clinical trials to determine whether maraviroc and similar CCR5-blocking drugs could help a person's immune system fight off Staph infections.